This application relates to the subject material simultaneously filed U.S. patent application Ser. No. 09/321,170, entitled xe2x80x9cGenetic Assay Systemxe2x80x9d, the disclosure of which is hereby incorporated by reference herein.
The present invention relates to methods, systems and apparatuses for accomplishing combinatorial processes, including synthesis screening and chemical diagnostic assays. More particularly, the invention relates to a system and method that utilizes a relatively small multiple fluid sample processor with detachable layers.
Traditional methods in the field of chemical and biological processes, are often slow and tedious. These include combinatorial chemistry, high-throughput screening assays and genomic synthesis for making, screening and/or testing potential new compounds and materials. In the pharmaceutical industry, for example, combinatorial chemistry for making series of compounds for testing potential new drug candidates are often complex, time-consuming and expensive. One of the underlying reasons in combinatorial chemistry is that each member of a series, or each potential drug compound, must be created and tested individually.
Traditionally, experiments are conducted by manually injecting reagent fluids or other agents into a multitude of vials or reaction tubes. Each vial is filled manually by a laboratory technician or by a robot processor. The solutions within each vial or reaction tube may differ only slightly from an enjoining vial so that permutations of the solution are investigated simultaneously. Often, receptors with fluorescent tags or other mechanisms for identifying each of the new compounds are included in the vial or reaction tube. This allows better identity of the compound and also allows computerization of the results.
Recently, the process has been improved with the introduction of robotics which automate the process of depositing materials into the multitude of vials and reaction tubes. However, the process continues to face problems in the area of cost and space requirements. With thousands of compounds being tested and in some cases incubated over long periods of time, the process requires a large quantity of space to house the multitude of trays of vials or reaction tubes. These apparatuses are currently large and cumbersome to handle. Furthermore, the process generally consumes a large quantity of reagents for testing thousands of compounds. The reagents and other materials used in the process are often expensive and difficult to obtain.
To reduce the cost and increase the efficiency of the system and processes, smaller reaction synthesizers have been utilized. These use smaller quantities of reagents. However, proper control and an effective delivery system are necessary for regulating and distributing the minute amounts of reagents to the reaction cells.
One apparatus for multiple simultaneous synthesis is shown, for example, in U.S. Pat. No. 5,324,483. A smaller device using microchannels which addresses some of the problems of size and cost, is shown, for example, in U.S. Pat. No. 5,603,351.
A need exists in the art for faster, more efficient and less costing multiple fluid sample processors, systems and methods for accomplishing the process of combinatorial chemistry, as well as other chemical and biological processes. A need also exists for automating the fluid sample processing and diagnostic processes, including use of robotic mechanisms and systems.
It is an object of the present invention to provide a new and improved multiple fluid sample processor, system and method, particularly for use in combinatorial chemistry, but also for use in any synthesis, catalyst discovery, process development, screening or diagnostic applications. It is another object of the present invention to create a relatively small device which can carry out hundreds and even thousands of chemical experiments simultaneously, create new compounds, and assess their impact on chemical or biological systems.
It is another object of the present invention to provide a liquid handling drug discovery and diagnostic tool which increases the speed and productivity of discovering new drug candidates and does so on a miniaturized scale or platform that reduces cost and manual handling. It is a further object of the present invention to provide a multiple fluid sample processor, system and method which is capable of conveying, transporting, and/or processing samples in a large multiplicity of sites without exposure to the atmosphere.
Other objects, purposes and advantages of the present invention will become apparent in the following description of the invention, particularly when viewed in accordance with the attached drawings and appended claims.
In accordance with the present invention, a multiple fluid sample processor, system and method are provided which utilizes a multi-layered fluidic array having microtiter scale reservoirs, connecting microchannels and sub-microtiter reaction or assay wells. A three-dimensional architecture of microchannels and nano-reaction vessels are constructed in one or more of the layers. The array incorporates a modular configuration with several distinct layers or plates. The device array can include an upper reservoir layer (or top feedthrough plate), a center distribution layer or plate, and a lower or bottom well (or reactor) layer or plate. Additional plates and layers could be utilized as needed or desired. The plates are stacked vertically and either permanently bonded or coupled together, preferably forming liquid-tight seals.
The upper reservoir layer provides feed-through channels and also serves as a cover for the device array. It contains apertures selectively positioned and connected to inlets located in the center distribution plate or layer. The apertures provide openings to fill the reservoirs with a plurality of reagents or other materials. The center distribution layer comprises a plurality of micro-sized reservoirs, channels, reservoir feeds, cell feeds, and overflow feeds, reset manifolds, and back-flow valves which are selectively formed in one or more bonded layers on the center distribution plate. The channels and reservoirs form a delivery system where reservoirs are grouped preferably into columns and rows. The reservoir layer and distribution layers can each comprise two or more plates or layers connected together in order to form and provide the requisite channels, reservoirs, and the like.
A detachable bottom layer or plate includes a plurality of submicrotiter reaction wells with a plurality of drain feeds. Once the proper agents or the materials are introduced into the reaction wells, the bottom plate may be processed while assembled, or can be decoupled from the display array and removed for incubation or analysis.
Pressurized fluid delivery mechanisms are utilized to distribute the reagents, solvents and other fluids to the array of channels and to fill the appropriate reservoirs. Micro-sized valves, such as capillary forming structures, are provided to allow orderly and efficient delivery and transport of fluid materials through the device. Various exhaust, capture and collection mechanisms and systems are provided for the materials once they are processed.